Genetic prediction of asthma increases multiple sepsis risks: A Mendelian randomization study.

ABSTRACT

Background: Observational epidemiological studies have indicated a potential association between asthma and sepsis, although the causal relationship between these 2 conditions remains uncertain. To further investigate this relationship, the present study utilized Mendelian randomization (MR) analysis approach to explore the potential links between asthma and various types of sepsis. Methods: In a large-scale genome-wide association study, single nucleotide polymorphisms (SNPs) associated with asthma were selected as instrumental variables. Three methods, including inverse-variance weighted (IVW), MR-Egger regression, and weighted median were used to assess the causal relationship between asthma and sepsis. The odds ratio (OR) and 95% confidence interval (CI) were used as the evaluation metrics for causal relationships, and sensitivity analysis was conducted to assess pleiotropy and instrument validity. Finally, a reverse MR analysis was conducted to investigate whether there is a causal relationship between sepsis and asthma. Results: We found a positive association between asthma and an increased risk of sepsis (OR=1.18, P＜0.05), streptococcal sepsis (OR=1.23, P=0.04), pneumonia-related sepsis (OR=1.57, P＜0.05), pneumococcal sepsis (OR=1.58, P=0.01), other sepsis (OR=1.15, P＜0.05), and sepsis in intensive care unit (ICU) settings (OR=1.23, P=0.02). Sensitivity analysis showed consistent results without heterogeneity or pleiotropy. The reverse MR analysis reveals no causal relationship between various types of sepsis and asthma. Conclusion: Our study demonstrates a causal relationship between asthma and different types of sepsis. These findings suggest the importance of healthcare providers paying attention to the potential risk of sepsis in asthma patients and implementing appropriate preventive and intervention measures in a timely manner.